|
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P170034 / PAS001 |
| Date Original Protocol Accepted |
11/18/2015
|
| Date Current Protocol Accepted |
|
| Study Name |
Continuation of Premarket Cohort PAS
|
| Device Name |
HYDRUS MICROSTENT
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Descriptive
|
| Study Population |
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
Continued follow-up PAS for the prospective, randomized, multicenter pivotal study (HORIZON Study, CP 11-001) conducted under IDE G110048 to collect additional long-term safety information. All available subjects in both the Hydrus Microstent and control groups who consented to continuation in the study will be followed 5 years postoperatively.
|
| Sample Size |
Of the 556 subjects treated in this study (369 Hydrus, 187 controls), 489 subjects (334 Hydrus, 157 controls) have completed 3-year evaluations. Based on the age of the study population and other factors, it is estimated that a minimum of 70% of subjects (233 Hydrus subjects and 110 control subjects) will complete 5-year postoperative evaluations in the continuation study.
|
| Key Study Endpoints |
Primary safety outcome (study eye):
Rate of occurrence of sight-threatening adverse events
Secondary safety outcomes (study eye):
Best Corrected Visual Acuity (BCVA)
Rate of occurrence of ocular adverse events
Slit lamp, gonioscopy and fundus findings
Visual field mean deviation (MD)
Central corneal thickness
Central corneal endothelial cell density (ECD)
Rate of occurrence of device malposition1
Rate of occurrence of device obstruction
Rate of occurrence of peripheral anterior synechiae (PAS)
Secondary effectiveness outcome:
Mean change in intraocular pressure (IOP)
Proportion of patients who are not using ocular hypotensive medications with a 20% or greater reduction in IOP from baseline in the HORIZON Study
1 Device malposition is considered an AE if there are associated clinical sequelae, for example: secondary surgical intervention to modify device position (i.e., repositioning or explantation), corneal endothelial touch by device, central ECL =30%, device obstruction requiring secondary surgical intervention, or chronic inflammation or irritation.
|
| Follow-up Visits and Length of Follow-up |
postoperative visits at 3,4 and 5 years
|
| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
556 subjects (331 US and 225 OUS)
|
| Actual Number of Sites Enrolled |
28 US and 17 OUS
|
| Patient Follow-up Rate |
Of the 556 participants in the intent-to-treat (ITT) cohort, 114 (61 Hydrus, 53 control) were missing at the 60-month visit due to death, withdrawal, or loss to follow-up. The frequency of missing participants has increased successively from 24 months to 60 months which is not unexpected since participants were originally consented for a 24-month follow-up for the pivotal trial. There are no remaining active participants. Overall 60-month accountability is 86.8% in the Hydrus and 77% in the
|
| Final Safety Findings |
The primary safety endpoint is the rate of sight-threatening adverse events (SAEs). At 60 months, the cumulative rate of SAEs is comparable between the two groups, 13/369 (3.5%) in Hydrus eyes vs. 8/187 (4.3%) in controls (difference = -0.8%, 95% CI -4.2% to 2.7%). There were no reports of BCVA loss =2 lines after 3 months in either group at 60 months; the cumulative rates were 1.9% (7/369) in the Hydrus group, 2.1% (4/369) control. Cystoid macular edema was reported in 2.4% (9/369) of the Hydrus group and 2.1% (4/187) of the control group.
The most common adverse event in the Hydrus group was peripheral anterior synechiae (PAS) with or without concomitant partial or complete device obstruction (14.6%; 54/369); 37% (20/54) of the PAS cases were with concomitant device obstruction. The rate of device obstruction was 8.4% (31/369), complete 2.4% (9/369), partial 6.0% (22/369). The rate of device malposition was 1.4% (5/369).There were no serious sequelae from these PAS and obstructive events. There were no explantations. The rate of persistent anterior uveitis in the Hydrus group was 0.5% (2/369) and in the control group 2.1% (4/187). Worsening of visual field (change in MD =2.5 dB on two repeated tests) was reported in 8.4% Hydrus (31/369) and 9.6% control (18/187). Secondary surgical intervention (SSI) to lower inadequately controlled IOP was performed in 4.9% Hydrus (18/369) and 7.5% control (14/187).
Corneal endothelial cell measurements were collected in three areas of the cornea (central, nasal, and temporal). Corneal edema was reported in 1.4% Hydrus (5/369) and 0.5% control (1/187). Mean central ECL at 60 months was -19% +/-16% Hydrus and -13%+/-13% control. Corneal endothelial cell loss (ECL) remains relatively stable in both groups after initial postoperative drops (in both groups). The frequencies of central ECL =30% and ECD<1000 cells/mm2 are higher in the Hydrus group (20.8% [62/298], 4.7% [14/298], respectively) versus control (10.6% [14/132], 0.8% [1/132], respectively). These patterns suggest that there is greater impact of the corneal endothelium from initial surgical trauma in the Hydrus group compared to the control group. The observed ECL did not manifest in clinically significant sequelae, with only one case of corneal decompensation requiring corneal transplantation (DMEK).
|
| Final Effect Findings |
Washed-out, diurnal IOPs were not performed at timepoints after Month 24, and hence the primary endpoint (proportion of eyes with unmedicated mean IOP reduction >20% from baseline) was not calculated at these later timepoints. After Month 24, there is a gradual decrease in the proportion of Hydrus participants who remain glaucoma medication-free, from 78.2% at Month 24 to 58.8% at Month 60. These numbers in the control group are lower (47.6% at Month 24 to 35.8% at Month 60). Among the Hydrus group participants who were medication-free, the mean IOP ranged from 16.5 to 16.7 mm Hg at Months 36, 48, and 60; among the control group participants who were medication-free, mean IOP ranged from 17.2 to 17.6 mm Hg at Months 36, 48, and 60.
A secondary effectiveness outcome is the proportion of participants who are not using IOP-lowering medications and who achieve greater than or equal to 20% IOP reduction from baseline. At 5 years, this endpoint was achieved in 48.4% of the Hydrus group (149/308) versus 25.4% of the control group (34/134).
|
| Study Strengths & Weaknesses |
The overall safety profile of the device over 5 years of follow-up remains good. The most common adverse event is peripheral anterior synechiae (PAS) with or without concomitant partial or complete device obstruction (14.6; 54/369); 37% (20/54) of the PAS cases were with concomitant device obstruction. The rates of complete and partial device obstructions were 2.4% and 6.0%, respectively. There have been no serious sequelae from these PAS and obstructive events, including no explantations. The rate of persistent anterior uveitis in the Hydrus was low (0.5%). Corneal endothelial cell loss (ECL) remains relatively stable in both groups after initial postoperative drops (in both groups), but the distribution of loss is different between the two groups. The frequency of central, nasal, and temporal ECL greater than or equal to 30% and ECD<1000 cells/mm2 is slightly higher in the Hydrus group versus control. These patterns suggest that there is greater impact of the corneal endothelium from initial surgical trauma in the Hydrus group compared to the control group. The observed ECL largely did not manifest in clinically significant sequelae, with only one case of corneal decompensation requiring corneal transplantation.
|
| Recommendations for Labeling Changes |
In addition to including all of the PAS results, the CoA is fulfilled with an August 20, 2020 email request in P170034-R003 to update label in a future labeling supplement:
The Hydrus Microstent is intended for implantation in conjunction with cataract surgery, which may impact corneal health. Therefore, caution is indicated in eyes with evidence of corneal compromise (e.g., Fuch’s dystrophy, corneal guttae or low endothelial cell density) or with risk factors for corneal compromise following cataract surgery (e.g., advanced age, dense nuclear sclerosis). In addition, glaucoma patients typically have larger endothelial cell losses from surgery than non-glaucoma patients. Therefore, surgeons should consider a patient’s specular microscopy endothelial cell density measurements to assess the risk of corneal decompensation after implantation of this device.
|
